Identification of genetic subtypes in follicular lymphoma

被引：6

作者：

Shelton, Victoria ^{[1
]}

Detroja, Rajesh ^{[1
]}

Liu, Ting ^{[1
]}

Isaev, Keren ^{[1
]}

Silva, Anjali ^{[1
,2
]}

Passerini, Verena ^{[3
]}

Bakhtiari, Mehran ^{[1
]}

Calvente, Lourdes ^{[1
]}

Hong, Michael ^{[1
]}

He, Michael Y. ^{[1
]}

Modi, Saloni ^{[1
]}

Hershenfeld, Samantha A. ^{[1
]}

Ludvigsen, Maja ^{[4
,5
]}

Madsen, Charlotte ^{[5
]}

Hamilton-Dutoit, Stephen ^{[6
]}

d'Amore, Francesco Annibale ^{[4
,5
]}

Brodtkorb, Marianne ^{[7
]}

Johnson, Nathalie A. ^{[8
]}

Baetz, Tara ^{[9
]}

LeBrun, David ^{[10
]}

Tobin, Josh W. D. ^{[11
,12
]}

Gandhi, Maher K. ^{[11
,12
]}

Mungall, Andrew J. ^{[13
]}

Xu, Wei ^{[14
]}

Ben-Neriah, Susana ^{[15
]}

Steidl, Christian ^{[15
]}

Delabie, Jan ^{[16
]}

Tremblay-LeMay, Rosemarie ^{[16
]}

Jegede, Opeyemi ^{[17
]}

Weigert, Oliver ^{[3
,18
,19
]}

Kahl, Brad ^{[20
]}

Evens, Andrew M. ^{[21
]}

Kridel, Robert ^{[1
]}

机构：

[1] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[2] Vector Inst, Toronto, ON, Canada

[3] Ludwig Maximilians Univ LMU Hosp, Dept Internal Med 3, Munich, Germany

[4] Aarhus Univ, Dept Clin Med, Aarhus, Denmark

[5] Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark

[6] Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark

[7] Oslo Univ Hosp, Dept Oncol, Oslo, Norway

[8] Jewish Gen Hosp, Montreal, PQ, Canada

[9] Queens Univ, Dept Oncol, Kingston, ON, Canada

[10] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada

[11] Mater Res Univ Queensland, Brisbane, Qld, Australia

[12] Princess Alexandra Hosp, Dept Haematol, Brisbane, Qld, Australia

[13] Canadas Michael Smith Genome Sci Ctr BC Canc, Vancouver, BC, Canada

[14] Univ Toronto, Princess Margaret Canc Ctr, Dalla Lana Sch Publ Hlth, Dept Biostat, Toronto, ON, Canada

[15] BC Canc, Vancouver, BC, Canada

[16] Univ Hlth Network, Lab & Med Program, Toronto, ON, Canada

[17] Dana Farber Canc Inst, Boston, MA USA

[18] German Canc Consortium DKTK, Munich, Germany

[19] German Canc Res Ctr, Heidelberg, Germany

[20] Washington Univ, St. Louis, MO USA

[21] Rutgers Canc Inst, New Brunswick, NJ USA

来源：

BLOOD CANCER JOURNAL | 2024年 / 14卷 / 01期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

HIGH-RISK; EXPRESSION; VALIDATION; MUTATIONS; CLASSIFICATION; TRANSFORMATION; PATHOGENESIS; PROGRESSION; ACTIVATION; PREDICTION;

D O I：

10.1038/s41408-024-01111-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.

引用

页数：13

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